title: Human CD271-positive melanoma stem cells associated with metastasis establish tumor heterogeneity and long-term growth.
abstract: Human melanoma is composed of distinct cell types reminiscent of neural crest derivatives and contains multipotent cells that express the neural crest stem cell markers CD271(p75(NTR)) and Sox10. When isolated from solid tumors by using a method that leaves intact cell surface epitopes, CD271-positive, but not CD271-negative, cells formed tumors on transplantation into nude or nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. These tumors fully mirrored the heterogeneity of the parental melanoma and could be passaged more than 5 times. In contrast, in more immunocompromised NOD/SCID/IL2rγ(null) mice, or in natural killer cell-depleted nude or NOD/SCID mice, both CD271-positive and CD271-negative tumor cell fractions established tumors. However, tumors resulting from either fraction did not phenocopy the parental tumors, and tumors derived from the CD271-negative cell fraction could not be passaged multiple times. Together, our findings identify CD271-positive cells as melanoma stem cells. Our observation that a relatively high frequency of CD271/Sox10-positive cells correlates with higher metastatic potential and worse prognosis further supports that CD271-positive cells within human melanoma represent genuine cancer stem cells.
authors.affiliation: Institute of Anatomy and Biostatistics Unit ISPM, University of Zurich, Zurich, Switzerland.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Civenni
authors.forename: Anne
authors.initials: A
authors.lastname: Walter
authors.forename: Nikita
authors.initials: N
authors.lastname: Kobert
authors.forename: Daniela
authors.initials: D
authors.lastname: Mihic-Probst
authors.forename: Marie
authors.initials: M
authors.lastname: Zipser
authors.forename: Benedetta
authors.initials: B
authors.lastname: Belloni
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Maries
authors.initials: M
authors.lastname: van den Broek
authors.forename: Lukas
authors.initials: L
authors.lastname: Sommer
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis*; D014183:Transplantation, Heterologous
chemical_list: C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor